Age-related involuntary loss of muscle mass and strength occurs during ageing and is called sarcopenia [1]. Regarding the degenerative loss of skeletal muscle mass, it occurs at a rate of 3-8% per decade after the age of 30 years and accelerate from 60 years of age. Both impaired muscle mass and muscle strength relate to age-related loss of muscle function.
The major drivers for maintenance of skeletal muscle mass are the stimulation of muscle protein synthesis and the inhibition of muscle protein breakdown. Muscle protein synthesis is stimulated by the bioavailability of amino acids (in particular of leucine) and physical activity.
Hence, both contribute to a positive net muscle protein balance (i.e. difference between muscle protein synthesis and protein breakdown; net muscle protein synthesis). It is important to maintain muscle mass and prevent muscle decline and muscle wasting. Protein starvation and muscle inactivity, which often occur with ageing and disease, result in a failure to maintain muscle mass, with muscle wasting. With ageing, an imbalance exists between muscle protein synthesis and breakdown. Moreover, the anabolic response to feeding decreases, which further contributes to an insufficient net muscle protein synthesis, and subsequent muscle decline with ageing. [1-6]. Compared to younger adults, elderly need higher levels of blood amino acids—especially leucine—to stimulate muscle protein synthesis. This phenomenon of reduced responsiveness of muscle that occurs in elderly, is called anabolic resistance which leads to muscle decline. Hence, it is beneficial to have a nutritional composition, especially for elderly, to overcome this resistance and stimulate (net) muscle protein synthesis. Indeed, a so called “fast” protein source with high leucine proved more effective in elderly than a similar protein amount with low leucine or a “slow” protein [7, 8]. Thus, an adequate anabolic stimulus to the muscle still has the potential to activate the muscle protein signalling pathway and thereby provoke muscle protein synthesis in a mammal, especially in an elderly mammal.
Specific amino acids are known for their stimulating effect on muscle protein synthesis; these amino acids are considered “anabolic”. Of the amino acids, essential amino acids (EAAs) in particular are able to stimulate muscle protein synthesis in the elderly, whereas non-EAAs may be of less benefit for muscle anabolism [9, 10]. Elderly require a higher dose of EAAs (>6.7 g EAAs), provided as a bolus, to stimulate muscle anabolism [11, 12]. Hence, the age-related lower responsiveness could also be overcome by increasing leucine intake (from 1.7 g to 2.8 g leucine in a mixture of 6.7 g EAAs) [8]. Leucine also acts as a signalling molecule [13]. The importance of leucine for muscle protein synthesis was also confirmed for intact protein sources with various levels of leucine (whey sources and casein) in an animal study. In this study, old rats showed a gradual increase in muscle protein synthesis concomitant with an increase of leucine level in the protein source, as is the case for whey protein [14]. In healthy elderly, whey protein also resulted in a higher whole body protein synthesis rate compared with casein protein [15].
Muscle protein synthesis is positively related to the extracellular amino acid concentration [16] and intracellular amino acid appearance in the muscle [17]. An increase in serum amino acid concentration may stimulate muscle protein synthesis, but higher levels of essential amino acids and especially leucine, are needed in the elderly [8, 11]. Therefore, strategies that can significantly increase blood leucine levels seem useful to help restore the acute anabolic response to feeding in elderly. Blood amino acid levels after feeding can be influenced by the type of food. Part of the dietary amino acids is extracted in the intestine and liver for local protein synthesis (i.e. splanchnic extraction or sequestration). The remaining amino acids appear in the systemic blood circulation and reach other organs, with the muscle as the largest protein reservoir [18]. Dietary proteins vary in amino acid composition, in rate of digestion, and in level of splanchnic extraction, all influencing the subsequent appearance of amino acids in the circulation. Because whey protein contains higher levels of leucine than casein protein, serum leucine levels are higher after intake of whey protein [15]. Previous studies comparing casein protein and whey protein identified casein as a “slow” protein and whey as a “fast” protein, referring to the rate of appearance in the circulation of the amino acids [7, 19]. The digestion rate is an important factor in this slow/fast concept [20] and is partly determined by the rate of gastric emptying. In elderly, the appearance of amino acids in the blood is reduced [15], because splanchnic extraction is higher [21, 22] and digestion/gastric emptying rate is slower [23] than in young.
Following the need for supplying higher levels of amino acids to increase the bioavailability of anabolic amino acids to stimulate muscle protein synthesis in a mammal, especially in an elderly human, serum amino acid levels in elderly after intake of a high whey-protein containing, low-caloric nutritional formulations were studied. The clinical study evaluated the bioavailability of amino acids in elderly after intake of such a nutritional formulation.